Eyes on cannabis #2: what is glaucoma?
Kia ora e hoa ma,
So far, our goal has been to understand the role of cannabis in glaucoma. But before we can dive into this interesting topic, we need to understand the fundamentals.
In last week's newsletter, we learned about the eye's basics: how we see and the eye's important functions in relations to glaucoma. Today, we will continue learning about glaucoma: what it is, why its important, and how it works.
Glaucoma is the 'silent thief of sight'. It is one of the major causes of visual impairment worldwide (Thylefors & Negrej, 1994). According to Blind Low Vision New Zealand, 91,000 Kiwi's have glaucoma, half of which do not know they have the disease. Visual impairment from glaucoma can make life difficult for an individual, so awareness of the disease is important.
What is Glaucoma?
From my experience, notoriety in glaucoma comes from the 'puff' test or 'pressure' test. The discomfort of having air blown into your eyes is so memorable that it stands as the hallmark test for glaucoma. Unfortunately, it's not that simple. The 'pressure' test, though important, is only one measurement used in the complex diagnosis of glaucoma.
Glaucoma is better described as a group of diseases, all of which are characterised in three ways (Thylefors & Negrej, 1994):
Damage to the optic nerve in the form of 'cupping'.
This damage results in progressive visual field loss.
This damage may or may not be related to intraocular pressure (IOP).
The simplest definition I give for glaucoma is where the connection between the eye the brain becomes damaged, resulting in loss of peripheral vision.
Glaucoma is challenging to diagnose. For an individual who potentially has the disease, they sit on a spectrum (Weinreb & Khaw, 2004):
Early stages, not being able to detect even with testing. This is where it is important to identify risk factors like family history, age and race, and be monitored more routinely.
Detectable with tests but without any symptoms. This is where routine clinical tests are paramount in closely monitoring the disease and whether or not treatment should be initiated or changed based on its effectiveness.
End-stage and symptoms become noticeable. This is beyond repair, where vision loss cannot be reversed, and treatment only aims to save what is left.
Symptoms only occur at the late stages of the disease, where treatment cannot bring back lost vision. Routine eye examinations are paramount in catching glaucoma early and monitoring those who have a family history.
Anyone at any age can have an eye examination, but Glaucoma New Zealand recommends an eye examination by the age of 45 (Glaucoma New Zealand, n.d.).
When determining the presence of glaucoma, we must adopt a detective's approach. We must gather clues to determine a guilty (or innocent) verdict. We do this by performing several different tests (Glaucoma Research Foundation, 2020). These tests can include:
our friend again, measuring eye pressure, which is called tonometry,
analysing the state of the optic nerve by looking into the eye, also known as ophthalmoscopy (additionally, photography and taking scans using optical coherence tomography [OCT] are used the document the condition of the optic nerve, which can be used as a comparison in the future) (Boston, 2020),
examining the peripheral vision — perimetry,
observing the drainage mechanism of the eye using gonioscopy,
looking at the thickness of cornea with pachymetry,
A collection of these tests' results is combined to determine glaucoma diagnosis. Not just eye pressure alone. Additionally, most of these tests need to be repeated over a period of time.
The many types of Glaucoma
Glaucoma is an umbrella term. There are different types and are classified by:
eye pressure: high or normal,
drainage angle: open or closed,
and if this angle is closed, the time of presentation: acute (sudden) or chronic (long-standing),
or if the angle is open, then eye pressure again: high or low,
cause of glaucoma: If a cause is present, then the glaucoma is secondary to this cause; if not, then this is considered primary
Here are some examples of glaucoma (National Eye Institute, 2020):
Normal-Tension Glaucoma (NTG) — normal eye pressure, but there is damage to the optic nerve typical of glaucoma.
Primary Open Angle Glaucoma (POAG) — high eye pressure, open-angle, no other causes.
Acute Angle Closure Glaucoma (AACG) — elevated eye pressure due to a closed drainage angle, severe pain, considered an ocular emergency.
Pseudo-exfoliation Glaucoma (PEX) — elevated eye pressure, open-angle, clumps of dandruff-like protein clogging the drainage angle, a secondary open-angle glaucoma.
Pigment Dispersion Syndrome (PDS) — elevated eye pressure, open-angle, pigment from the iris has rubbed off, accumulating at the drainage angle, a cause and thus secondary open-angle glaucoma.
Neovascular Glaucoma — elevated eye pressure resulting from irregular blood vessels growing and blocking the eye's drainage angle, a secondary glaucoma.
There are many other examples. Performing the aforementioned tests can determine what type of glaucoma a patient is suffering from. Knowing what type will affect the treatment method.
How Glaucoma does its damage
Remember, the optic nerve's primary role is to relay sensory information from the eye to the brain. Glaucoma is when the optic nerve becomes damaged, and its ability to perform its primary responsibility becomes diminished. This results in vision loss — more specifically, peripheral vision loss.
How does this damage occur?
There are three proposed mechanisms, which may be independent or working in parallel (Gupta et al., 2009):
Mechanical theory: increased eye pressure (from some cause such as a blocked drainage angle) causes mechanical damage to the optic nerve structure called the lamina cribosa. Imagine the optic nerve is a cable. The wires running through this cable are called axons. Axons are part of the retinal ganglion cells (RGCs), responsible for relaying the information from the retina to the brain. Sense turns into perception. The axons also facilitate the flow of a signalling chemical called neurotrophin in the opposite direction, from the brain to retinal ganglion cells. These axons pass through the lamina cribosa when approaching the brain. Elevated eye pressure results in deformation of the lamina cribosa. This damaged the axons leads to restricted flow of neurotrophin. Lack of neurotrophin results in RGCs performing **apoptosis (**or programmed cell death). Loss of RGCs means less visual information reaches the brain. This manifests as visual field loss and change in the appearance of the optic nerve.
Vascular theory: Another proposed mechanism involves reduced blood flow to the vessels that nourish the optic nerve. A healthy optic nerve and retina require consistent and good blood flow or perfusion. Age results in reduced blood perfusion. In addition to this, increased sensitivity to endothelin-1 (a chemical signal that causes blood vessels to constrict — reducing blood flow), characteristic of diseases with reduced blood flow, is associated with glaucoma, along with migraines. The lack of stable and reliable blood supply results in RGC death. And hence, loss of vision.
Glutamate theory: Elevated levels of glutamate surrounding the retina can cause apoptosis of retinal ganglion cells. Glutamate is a neurotransmitter or a molecule that is responsible for sending signals between nerve cells. High levels of glutamate are toxic to surrounding cells, leading to cell death. This mechanism is controversial since some studies indicate no changes in glutamate levels. Also, apoptosis results in high glutamate levels; this mechanism may be in sequence with the previous two.
Other mechanisms include:
Nitric oxide (NO): NO freely enter cells. NO can react with cell metabolites resulting in highly oxidative molecules. Oxidative molecules or free radicles are toxic to the cells internal components. An excess of these can damage the cell and, ultimately, the cell's death and destruction.
Oxidative stress: Glutathione and ascorbic acids are both present in the tissues of the eyes. They are very effective in reducing oxidative stress. In the case of poor blood flow, levels of these molecules can drop, resulting in the eye being more susceptible to oxidative stress. Like with increased NO, this can result in cell death.
Conclusion
To understand the role of cannabis and glaucoma, we must understand what glaucoma is and how it leads to vision loss. In a previous newsletter, we learned about how the eye sees and the eye's relevant functions concerning glaucoma.
More than a simple 'puff' test, glaucoma is defined as optic nerve damaged with associated visual field loss that may or may not result from elevated intraocular (eye) pressure. Diagnosis is not so straightforward, requiring multiple tests. These do include eye pressure but also visual fields, assessment of the optic nerve, checking the eye's drainage angle, and corneal thickness.
When untreated, glaucoma causes visual impairment, significantly reducing one's quality of life. In the beginning, there are no symptoms. We rely on consistent eye exams with an eye care professional as the only way to determine if glaucoma is present.
Glaucoma is an umbrella for many different types. We use testing to determine which type. For example, a high eye pressure that presents acutely with a closed angle is likely to be acute angle-closure glaucoma. Another example is normal eye pressure, but there is optic nerve damage typical of glaucoma — normal-tension glaucoma.
The mechanism of vision loss in glaucoma is contested with three mechanisms: mechanical damage from high eye pressure resulting in further damage to the cables that send visual information from the eye to the brain; lack of blood supply to these cables; and toxic accumulation of glutamate resulting in the communication cells committed programmed cell death.
In the next newsletter, we are going to look at current and common treatments for glaucoma. Please stay tuned. Thank you for reading. If you have any feedback, hit reply — I'm listening.
Other than that, did you find this useful? If you did, please forward this to family and friends to find it useful too.
Thanks for reading, and all the best for the week ahead.
Ngā mihi nui,
Shivan :)
References
To be provided in a future blog post.
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